Emerging links between type 2 diabetes and Alzheimer’s disease

Abstract

Type 2 diabetes mellitus and Alzheimer’s disease are both associated with increasing age, and each increases the risk of development of the other. Epidemiological, clinical, biochemical and imaging studies have shown that elevated glucose levels and diabetes are associated with cognitive dysfunction, the most prevalent cause of which is Alzheimer’s disease. Cross sectional studies have clearly shown such an association, whereas longitudinal studies are equivocal, reflecting the many complex ways in which the two interact. Despite the dichotomy, common risk and etiological factors (obesity, dyslipidemia, insulin resistance, and sedentary habits) are recognized; correction of these by lifestyle changes and pharmacological agents can be expected to prevent or retard the progression of both diseases. Common pathogenic factors in both conditions span a broad sweep including chronic hyperglycemia per se, hyperinsulinemia, insulin resistance, acute hypoglycemic episodes, especially in the elderly, microvascular disease, fibrillar deposits (in brain in Alzheimer’s disease and in pancreas in type 2 diabetes), altered insulin processing, inflammation, obesity, dyslipidemia, altered levels of insulin like growth factor and occurrence of variant forms of the protein butyrylcholinesterase. Of interest not only do lifestyle measures have a protective effect against the development of cognitive impairment due to Alzheimer’s disease, but so do some of the pharmacological agents used in the treatment of diabetes such as insulin (especially when delivered intranasally), metformin, peroxisome proliferator-activated receptors γ agonists, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes must be recognized as a risk for development of Alzheimer’s disease; clinicians must ensure preventive care be given to control and postpone both conditions, and to identify cognitive impairment early to manage it appropriately.

Keywords: Cognition; Insulin resistance; Insulin; Butyrylcholinesterase; Dementia

Core tip: Type 2 diabetes mellitus is a risk factor for future development of Alzheimer’s disease, the most prominent cause of cognitive failure in the elderly. Common pathogenic mechanisms underpin both conditions. Therapeutic strategies in prevention (lifestyle changes) and pharmacological agents (biguanides, intranasal insulin, thiazolidinediones, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors could also be useful against Alzheimer’s disease.